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Curated Papers > Highly Cited Authoritative Literature on "Tumor Microenvironment"

The Tumor Microenvironment Innately Modulates Cancer Progression. ​

Literature Information ​

DOI10.1158/0008-5472.CAN-18-3962
PMID31350295
JournalCancer research
Publication Year2019
Times Cited1808
KeywordsTumor Microenvironment, Cancer Progression, Immune Cells
Literature TypeJournal Article, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, Non-P.H.S., Review
ISSN0008-5472
Pages4557-4566
Issue79(18)
AuthorsDominique C Hinshaw, Lalita A Shevde

TL;DR ​

This research highlights the role of both innate and adaptive immune cells in shaping the tumor microenvironment (TME), which influences cancer progression through interactions with cancer cells. By elucidating this complex communication, the study suggests that targeting multiple components of the TME could enhance therapeutic strategies and improve patient outcomes.

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Tumor Microenvironment · Cancer Progression · Immune Cells

Abstract ​

Cancer development and progression occurs in concert with alterations in the surrounding stroma. Cancer cells can functionally sculpt their microenvironment through the secretion of various cytokines, chemokines, and other factors. This results in a reprogramming of the surrounding cells, enabling them to play a determinative role in tumor survival and progression. Immune cells are important constituents of the tumor stroma and critically take part in this process. Growing evidence suggests that the innate immune cells (macrophages, neutrophils, dendritic cells, innate lymphoid cells, myeloid-derived suppressor cells, and natural killer cells) as well as adaptive immune cells (T cells and B cells) contribute to tumor progression when present in the tumor microenvironment (TME). Cross-talk between cancer cells and the proximal immune cells ultimately results in an environment that fosters tumor growth and metastasis. Understanding the nature of this dialog will allow for improved therapeutics that simultaneously target multiple components of the TME, increasing the likelihood of favorable patient outcomes.

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Primary Questions Addressed ​

  1. How do specific cytokines and chemokines secreted by cancer cells alter the function of surrounding stromal cells in the tumor microenvironment?
  2. What role do innate immune cells play in the reprogramming of the tumor microenvironment, and how does this influence cancer progression?
  3. In what ways can targeting the interactions between cancer cells and immune cells within the tumor microenvironment improve therapeutic outcomes for patients?
  4. How does the presence of different types of immune cells in the tumor microenvironment affect the metastatic potential of cancer cells?
  5. What are the implications of understanding the cross-talk between cancer cells and immune cells for developing combination therapies in cancer treatment?

Key Findings ​

Research Background and Purpose ​

The tumor microenvironment (TME) plays a critical role in cancer progression and metastasis. This review discusses how cancer cells alter their surrounding stroma and the significant contributions of both innate and adaptive immune cells in this process. The authors aim to provide insights into the interplay between tumor cells and immune cells, highlighting the potential for therapeutic strategies that target multiple components of the TME.

Main Methods/Materials/Experimental Design ​

The review synthesizes existing literature on the roles of various immune cells in the TME, focusing on their interactions with tumor cells. The authors categorize immune cells into innate (e.g., macrophages, neutrophils, dendritic cells, myeloid-derived suppressor cells, natural killer cells) and adaptive (e.g., T cells, B cells) and describe their contributions to tumor progression.

Mermaid diagram

Key Results and Findings ​

  1. Macrophages: They can be polarized into M1 (pro-inflammatory) and M2 (immunosuppressive) phenotypes. M2 macrophages are prevalent in the TME and are associated with poor prognosis in various cancers.
  2. Dendritic Cells (DCs): They are crucial for initiating T-cell responses. However, in the TME, they often adopt a tolerogenic phenotype, reducing their effectiveness in activating immune responses.
  3. Neutrophils: They can exhibit either tumor-suppressive (N1) or tumor-promoting (N2) functions depending on the tumor stage. Their role in promoting metastasis is highlighted through mechanisms like extracellular trap formation.
  4. Myeloid-Derived Suppressor Cells (MDSCs): These cells suppress immune responses and facilitate tumor progression. They contribute to creating a premetastatic niche.
  5. Natural Killer (NK) Cells: While they have potent cytotoxic capabilities, their functions are often inhibited within the TME.

Main Conclusions/Significance/Innovation ​

The review emphasizes the complexity of the TME and its influence on immune cell behavior, which ultimately impacts cancer progression. The authors advocate for therapeutic strategies that not only target tumor cells but also reprogram the immune components of the TME. This dual approach could enhance treatment efficacy and improve patient outcomes.

Research Limitations and Future Directions ​

The review identifies several limitations in current research, including the heterogeneity of immune cell populations in different tumor types and the need for more effective strategies to manipulate the TME. Future research should focus on:

  • Developing therapies that can selectively enhance the anti-tumor functions of immune cells while mitigating their immunosuppressive roles.
  • Exploring combination therapies that target multiple immune pathways and cell types within the TME.
  • Investigating the impact of the extracellular matrix and stromal components on immune cell behavior and tumor dynamics.

In summary, understanding the interactions within the TME presents a promising avenue for developing more effective cancer therapies.

References ​

  1. Natural cytotoxic activity of peripheral-blood lymphocytes and cancer incidence: an 11-year follow-up study of a general population. - K Imai;S Matsuyama;S Miyake;K Suga;K Nakachi - Lancet (London, England) (2000)
  2. Pathogen-specific regulatory T cells provoke a shift in the Th1/Th2 paradigm in immunity to infectious diseases. - Peter McGuirk;Kingston H G Mills - Trends in immunology (2002)
  3. Tolerogenic dendritic cells. - Ralph M Steinman;Daniel Hawiger;Michel C Nussenzweig - Annual review of immunology (2003)
  4. A paracrine loop between tumor cells and macrophages is required for tumor cell migration in mammary tumors. - Jeffrey Wyckoff;Weigang Wang;Elaine Y Lin;Yarong Wang;Fiona Pixley;E Richard Stanley;Thomas Graf;Jeffrey W Pollard;Jeffrey Segall;John Condeelis - Cancer research (2004)
  5. Macrophages promote the invasion of breast carcinoma cells via a colony-stimulating factor-1/epidermal growth factor paracrine loop. - Sumanta Goswami;Erik Sahai;Jeffrey B Wyckoff;Michael Cammer;Dianne Cox;Fiona J Pixley;E Richard Stanley;Jeffrey E Segall;John S Condeelis - Cancer research (2005)
  6. Breast cancer instructs dendritic cells to prime interleukin 13-secreting CD4+ T cells that facilitate tumor development. - Caroline Aspord;Alexander Pedroza-Gonzalez;Mike Gallegos;Sasha Tindle;Elizabeth C Burton;Dan Su;Florentina Marches;Jacques Banchereau;A Karolina Palucka - The Journal of experimental medicine (2007)
  7. Dendritic cell vaccines in melanoma: from promise to proof? - W J Lesterhuis;E H J G Aarntzen;I J M De Vries;D H Schuurhuis;C G Figdor;G J Adema;C J A Punt - Critical reviews in oncology/hematology (2008)
  8. Type I NKT cells protect (and type II NKT cells suppress) the host's innate antitumor immune response to a B-cell lymphoma. - Gourapura J Renukaradhya;Masood A Khan;Marcus Vieira;Wenjun Du;Jacquelyn Gervay-Hague;Randy R Brutkiewicz - Blood (2008)
  9. Tumor-targeted interferon-alpha delivery by Tie2-expressing monocytes inhibits tumor growth and metastasis. - Michele De Palma;Roberta Mazzieri;Letterio S Politi;Ferdinando Pucci;Erika Zonari;Giovanni Sitia;Stefania Mazzoleni;Davide Moi;Mary Anna Venneri;Stefano Indraccolo;Andrea Falini;Luca G Guidotti;Rossella Galli;Luigi Naldini - Cancer cell (2008)
  10. The Janus face of dendritic cells in cancer. - N Chaput;R Conforti;S Viaud;A Spatz;L Zitvogel - Oncogene (2008)

Literatures Citing This Work ​

  1. High Expression of TTYH3 is Related to Poor Clinical Outcomes in Human Gastric Cancer. - Subbroto Kumar Saha;Polash Kumar Biswas;Minchan Gil;Ssang-Goo Cho - Journal of clinical medicine (2019)
  2. Inducible nitric oxide synthase-derived extracellular nitric oxide flux regulates proinflammatory responses at the single cell level. - Veena Somasundaram;Anne C Gilmore;Debashree Basudhar;Erika Mariana Palmieri;David A Scheiblin;William F Heinz;Robert Y S Cheng;Lisa A Ridnour;Grégoire Altan-Bonnet;Stephen J Lockett;Daniel W McVicar;David A Wink - Redox biology (2020)
  3. Transforming Growth Factor-β Signaling Pathway in Colorectal Cancer and Its Tumor Microenvironment. - Yoshiro Itatani;Kenji Kawada;Yoshiharu Sakai - International journal of molecular sciences (2019)
  4. Antitumor Effect of a Novel Spiro-Acridine Compound is Associated with Up-Regulation of Th1-Type Responses and Antiangiogenic Action. - Daiana K Frade Silva;Sâmia S Duarte;Thaís M H Lisboa;Rafael C Ferreira;Ana Luíza de O Lopes;Deyse C M Carvalho;Sandra Rodrigues-Mascarenhas;Patricia Mirella da Silva;Miguel A S Pinheiro Segundo;Ricardo O de Moura;Karina C P Medeiros;Marianna V Sobral - Molecules (Basel, Switzerland) (2019)
  5. Current Strategies to Target Tumor-Associated-Macrophages to Improve Anti-Tumor Immune Responses. - Clément Anfray;Aldo Ummarino;Fernando Torres Andón;Paola Allavena - Cells (2019)
  6. Exosomes in Bone Sarcomas: Key Players in Metastasis. - Mariona Chicón-Bosch;Oscar M Tirado - Cells (2020)
  7. Immunomodulatory Roles of PARP-1 and PARP-2: Impact on PARP-Centered Cancer Therapies. - José Yélamos;Lucia Moreno-Lama;Jaime Jimeno;Syed O Ali - Cancers (2020)
  8. PLAG Exerts Anti-Metastatic Effects by Interfering with Neutrophil Elastase/PAR2/EGFR Signaling in A549 Lung Cancer Orthotopic Model. - Guen Tae Kim;Kyu Woong Hahn;Sun Young Yoon;Ki-Young Sohn;Jae Wha Kim - Cancers (2020)
  9. Modulation of tumor microenvironment for immunotherapy: focus on nanomaterial-based strategies. - Yun Liu;Jianfeng Guo;Leaf Huang - Theranostics (2020)
  10. Loss of S6K1 But Not S6K2 in the Tumor Microenvironment Suppresses Tumor Growth by Attenuating Tumor Angiogenesis. - Seul Lee;Hyun-Soo Roh;Seong-Soo Song;Jimin Shin;Jangchoon Lee;Dong Ha Bhang;Byung Gak Kim;Sung Hee Um;Han-Sin Jeong;Kwan-Hyuck Baek - Translational oncology (2020)

... (1798 more literatures)

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